In this single-center retrospective study, we enrolled 106 consecutive patients who underwent DP at Gifu University Hospital between January 2010 and December 2021. All procedures were conducted by expert surgeons who had qualified through the board certification system of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). We excluded 51 patients in total (tumor histopathology other than adenocarcinoma, n = 42; simultaneous resection of other organs, n = 9), and a total of 55 patients with primary PC were included in this study (Figure 1). We conducted our study in accordance with the World Medical Association Declaration of Helsinki and the study was approved by the Ethics Committee of Gifu University (approval number: 2021-026).
Patient characteristics were classified into three categories: pre-, intra-, and post-operative factors (Figure 2). First, the preoperative 11 factors were age, sex, BMI, diabetes mellitus, serum albumin level, tumor marker level (carcinoembryonic antigen [CEA] and carbohydrate antigen 19-9 [CA19-9]), preoperative chemotherapy, tumor size, tumor location, and pancreas-to-muscle signal intensity ratio on T1-weighted magnetic resonance imaging (MRI). Secondly, intraoperative 6 factors included operative time, blood loss, surgical procedure (open or laparoscopic surgery), pancreatic resection procedure (hand-sewn or stapler), pancreas texture (soft or hard), and pancreas thickness measured intraoperatively on resection site. Finally, postoperative 6 factors included the amylase levels of drainage fluid and serum (D-Amy and S-Amy), the white blood cell (WBC) count, C-reactive protein (CRP) level, body temperature, and heart rate on postoperative day (POD) 1 and 3.
Regarding DP for PC, regional lymph node dissection with splenectomy in accordance with the classification of pancreatic carcinoma of the Japan Pancreas Society , and pancreatic resection on the portal vein were performed. Pancreatic resection is performed with hand-sewn closure or using a linear stapler.
Among hand-sewn closure group, the pancreas was resected after the identification of the main pancreatic duct, and main pancreatic duct was ligated with a 3-0 silk suture. The stump of the remnant pancreas was closed with vertical mattress suture using 5-0 polypropylene. Among the group that underwent pancreatic resection using a linear stapler, the pancreas was resected using Endo GIA™ Tri-Staple or Signia™ stapling system (Medtronic plc., Dublin, Ireland) with a purple or black cartridge. The closure jaw was clamped carefully and slowly, taking 5 minutes at a fixed speed. The firing was performed at a speed of 1 cm per minute by firmly fixing the stapler. After firing, the jaws of the stapler were held shut for 1 minute. One 19Fr. Blake silicon drain (Johnson and Johnson Inc. New Brunswick, NJ, US) was placed near the stump of the remnant pancreas. The drain was to be removed on POD 4-5 when the drainage fluid was clear and postoperative course could pose no problem. The D-Amy and S-Amy level were measured on POD 1, 3, and 5. All patients received prophylactic antibiotics (cefmetazole) only intraoperatively or for 2 days postoperatively.
Pancreas-to-muscle signal intensity ration on T1-weighted MRI
Previously, we studied the potential value of preoperative MRI in evaluating pancreatic properties [33, 34] and reported that the pancreas-to-muscle signal intensity ratio on T1-weighted MRI (SIR on T1-w MRI) significantly correlated with pancreatic fibrosis, and that it may be a potential biomarker for predicting POPF. The signal intensity of the pancreatic parenchyma on the portal vein and the paraspinal muscle was measured using fat-suppressed axial T1-weighted imaging (Figure 3). The pancreas-to-muscle SIR on T1-w MRI was calculated using the following equation: [SI of the pancreatic parenchyma] / [SI of the paraspinal muscle].
Definition of POPF
In this study, we only included clinically symptomatic POPF. Therefore, only grades B and C pancreatic fistulas were defined as POPF (Grade B, symptomatic fistula requiring therapeutic intervention such as antibiotics and percutaneous drainage; Grade C, symptomatic fistula associated with a severe general condition of patients, sepsis, and multiorgan failure requiring aggressive treatment in the intensive care unit and surgical intervention), based on International Study Group of Pancreatic Fistula (ISGPF) definitions . Diagnosis day of POPF was defined as the date when intra-abdominal fluid collection with positive cultures was identified by ultra-sonography (US) or computed tomography (CT).
Continuous variables are expressed as median (range) values, and categorical variables are expressed as frequencies (percentages). For comparisons of variables between the POPF and non-POPF groups, a Fisher’s exact test was used for categorical variables, and a Mann-Whitney U test was used for continuous variables. The predictive ability for POPF after DP for PC was assessed by calculating the area under the receiver operating characteristic (ROC) curve. Youden’s index was used to determine the optimal cut-off value to calculate both specificities and sensitivities in the ROC curve analysis. The variables identified as potentially significant by univariate analysis were selected for multivariate analysis with a logistic regression model to identify the independent predictors of POPF after DP for PC. The limit of statistical significance for all analyses was defined as a 2-sided p-value of 0.05. All statistical analyses were performed using JMP software (SAS Institute Inc., Cary, NC, USA).